Infliximab improves vascular stiffness in patients with rheumatoid arthritis

Abstract

Objectives:Patients with rheumatoid arthritis (RA) have increased cardiovascular mortality. Tumour necrosis factor α (TNFα)-blocking therapy has been shown to reduce RA disease activity measures and joint damage progression. Some observational studies suggest that TNFα blockade reduces mortality and incidence of first cardiovascular events. The mechanisms contributing to these outcomes are unclear. This study assessed the effects of infliximab treatment on vascular stiffness and structure in patients with RA.Methods:A post hoc analysis of longitudinal data from a randomised placebo controlled study evaluated the effect of infliximab on vascular assessments. 26 patients received intravenous infliximab (3 mg/kg) at weeks 0, 2, 6 and every 8 weeks thereafter to week 54. Patients were followed up to 56 weeks of infliximab therapy with assessments of RA disease activity, cardiovascular risk factors, vascular stiffness (pulse wave velocity (PWV)), carotid intima media thickness (CIMT) and carotid artery plaque (CAP). Univariate analyses of changes over time by repeated measures analysis of variance (ANOVA) were followed by multivariate time-series regression analysis (TSRA) if changes were seen.Results:PWV was significantly lower (better) after 56 weeks of treatment with infliximab (ANOVA p<0.01, TSRA p<0.01). However, CIMT (ANOVA p = 0.50) and CAP (χ2 = 4.13, p = 0.88) did not change over the study period. Multiple cardiovascular risk measures did not change with treatment and did not correlate with changes in measures of vascular structure.Conclusions:Arterial stiffness improves with infliximab treatment in RA. This change may help explain the improved cardiovascular disease survival in patients with RA receiving TNFα-blocking therapy.

Tumor Necrosis Factor-α Antagonists Improve Aortic Stiffness in Patients With Inflammatory Arthropathies

“…Although one recently published study reported that treatment with etanercept reduced AIx, 31 our result is in agreement with the majority of previous investigations exploring the effect of TNF-␣ antagonists on AIx. 11,16,22,32 AIx is a composite measure dependent on the magnitude and site of pulse wave reflection in addition to the speed of the reflected wave. Peripheral vasodilatation is a well-known feature of infectious diseases, such as septicaemiae, induced among others by TNF-␣.…”

“…Indeed, reports from Swedish and British biological registers indicate that anti-TNF-␣ therapy reduces the incidence of cardiovascular events in patients with RA. 19,20 Moreover, treatment with TNF-␣ antagonists is reported by a few small studies to improve endothelial function and aortic stiffness in patients with RA 11,21,22 and microvascular function in patients with AS. 14 Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, is considered the current gold standard for measuring arterial stiffness.…”

Serum Levels of Matrix Metalloproteinase (MMP) 9, a Risk Factor for Acute Coronary Syndrome, Are Reduced Independently of Serum MMP-3 by Anti-TNF-^|^alpha; Antibody (Infliximab) Therapy in Patients With Rheumatoid Arthritis

“…This inhibition has been ascribed to the improvement of insulin resistance (11), endothelial function (12), and arterial wall stiffness (13). Anti-TNF-α blockades are associated with the reduction of carotid intima-media thickness (14), and the induction of hyperadiponectinemia (15).…”

Atherosclerosis in Patients with Rheumatoid Arthritis

“…In a post hoc analysis of longitudinal data from a randomized placebo controlled study also showed that infliximab therapy was associated with an improvement of arterial stiffness as measured by pulse wave velocity (PWV), but not carotid IMT and carotid artery plaque, in patients with RA (n=26) [89]. Further, 1-year treatment with anti-TNFα therapy has been shown to improve both PWV and carotid IMT in patients with inflammatory arthropathies [90].…”